Drug abuse is an important route of exposure for HIV-1. Both methamphetamine and lentiviral infections cause neurotoxicity and immunosuppression. However, the interactions between HIV-1 and methamphetamine in neurologic disease progression remain unclear. Part of the reason for this lack of information is that gathering data in people is particularly difficult, given the populations that engage in drug abuse. Additionally, invasive investigative measures are not possible in people. Thus, there is a pressing need for appropriate animal models to examine the role of methamphetamine on lentivirus disease progression, particularly the CNS form of the disease. We have now developed the feline/FIV model as a legitimate system for the study lf lentivirus induced neurologic disease. We have now developed the feline/FIV model as a legitimate system for the study of lentivirus induced neurologic disease. Not only does FIV produce a disease that is very similar to human AIDS, but it is also similar to HIV at both the molecular and biochemical levels. Numerous parameters have been established to monitor the effects ov irus injection on the CNS. We now want to apply this model to understand the potential interactions that methamphetamine may have with the neurological form of this lentivirus induced disease. In this proposed project. we plan to examine the in vitro effects of methamphetamine on the replication and transcriptional efficiency of FIV as well as investigate the outcome of methamphetamine schedule on FIV disease progression, by comparing the effects of administering methamphetamine in a single injection, multiple acute injections, and chronic administration. In order to better understand the effects of drug abuse on lentiviral disease progression, it is critical to have a model system that is pertinent, yet amenable to thorough testing and evaluation. As the smallest model for the study of natural lentivirus infections, the FIV/cat system provides the most economical and useful system for evaluating the effects of methamphetamine on lentivirus induced disease. The long-term objective of this proposal is to fully develop the FIV/cat system into a predictive animal model for assessing the effects of illicit drug use on the neurological form of this lentivirus induced disease.